The non-Alzheimer dementias include Pick's disease, Frontal Temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy, corticobasal degeneration, Parkinson's dementia complex of Guam and dementia without specific histological features. Our group has been working on these rare disease (which together, probably affect about 1/4 of the number of AD sufferers: that is ~500,000 Americans). Our intention is to elucidate the mechanisms of these diseases through genetic analysis so that we can model them in cells and animals as we and others have successfully done in Alzheimer's disease. In addition, since many of these diseases share pathological features, especially tangles, with Alzheimer's disease, these genetic analyses and the models we make using the genetic information, is of value in elucidating the pathgenic mechanisms in Alzheimer's disease. Our group was part of the consortium which showed that mutations in the tau gene caused Pick's disease/FTDP-17 and that showed that tau was a predisposing locus for PSP and CBD and we continue to look for new tau mutations and for families with frontal dementia in which tau is not the pathogenic locus. Of particular note: this year we have completely defined the extent of the tau haplotype, limiting the region in which we know that genetic variability which predisposes to PSP and CBD occurs .